This project proposes to systematically study relationships between neuroleptic properties of phenothiazine tranquilizers and their side chain conformations. To this end a large number of rigid structures will be synthesized wherein the side chains are held in various fixed conformations. Ring fusion isomers will be separated by chromatographic techniques and their structures confirmed by nuclear magnetic resonance and/or circular dichroism. The target compounds will be evaluated for neuroleptic activities in experimental animals and for central antidopaminergic and anticholinergic activities in vivo.